The objective of these studies is to determine the physiologic factors that regulate or influence secretion of insulin and glucagon by the islet cells of the pancreas. Using the perfused rat pancreas, isolated rat pancreatic islets, or cultured rat pancreatic cells, studies planned include: (1) the effects of enteric and pancreatic hormones on insulin and glucagon secretion, (2) the isolation and determination of the structure of enteric hormones with potent insulin-releasing activity, (3) the effects of stimulators and inhibitors of insulin and glucagon secretion on pancreatic islet adenyl cyclase, (4) the effects of hormones and neurotransmitters on growth and secretory capacity of cultured pancreatic alpha and beta cells, and (5) investigation of the multiple forms of somatostatin in tissues and secretions of the pancreas. This work may provide important information regarding the function of the endocrine cells of the pancreas and intestine. Knowledge of how these cells function may lead to a better understanding of the causes and optical treatment of diseases such as diabetes mellitus, islet cell tumors, and certain kinds of hypoglycemia.